Study Evaluating Efficacy / Safety of Etanercept + Methotrexate Compared to Usual Treatment in Moderate RA Subjects

This study has been terminated.
Sponsor:
Information provided by:
Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT00706797
First received: June 25, 2008
Last updated: June 16, 2011
Last verified: June 2011
  Purpose

To assess comparative radiographic efficacy, clinical efficacy and safety of etanercept (ETN) + methotrexate (MTX) with usual disease-modifying anti-rheumatic drug (DMARD) treatment in subjects with moderate RA who were treated with MTX monotherapy, but continue to have moderate disease activity.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: etanercept (EnbrelTM)
Drug: methotrexate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized Study to Evaluate the Radiographic Efficacy and Safety of Enbrel™ (Etanercept) Added to Methotrexate in Comparison With Usual Treatment in Subjects With Moderate Rheumatoid Arthritis Disease Activity

Resource links provided by NLM:


Further study details as provided by Wyeth is now a wholly owned subsidiary of Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Modified Total Sharp Score (TSS) at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.


Secondary Outcome Measures:
  • Change From Baseline in Erosions at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

  • Change From Baseline in Joint Space Narrowing at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Joint space narrowing score (a component of the modified TSS) is a measure of change in joint health. Joint space narrowing score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

  • Percentage of Participants Showing no Radiographic Progression (TSS Change <0.5) at Week 52 [ Time Frame: Baseline, Week 52, Last observation carried forward (LOCF) ] [ Designated as safety issue: No ]
    Radiographic non-progression determined based on TSS change <0.5 using the dichotomous response Yes / No. The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

  • Percentage of Participants Achieving >1.2 Improvement in Disease Activity Score Based on a 28-joint Count (DAS28) [ Time Frame: Baseline, Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]
    Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using Visual Analog Scale (VAS); range 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 square root (√) (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.1=higher disease activity; <3.2=low disease activity; <2.6=clinical remission. Achievement of >1.2 improvement defined as decrease in DAS28 >1.2 (change in DAS28 < -1.2).

  • Percentage of Participants Achieving Remission (DAS28 <2.60) [ Time Frame: Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]
    Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.

  • Percentage of Participants Achieving Low Disease Activity (DAS28 ≤3.20) [ Time Frame: Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]
    Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.

  • Percentage of Participants Achieving a >0.6 Disease Activity Score (DAS)28 Response [ Time Frame: Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]
    Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and participant's assessment of general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission. DAS28 response of >0.6 defined as decrease in DAS28 >0.6 (change in DAS28 < -0.6).

  • Percentage of Participants Achieving Moderate or Good Response on European League Against Rheumatism (EULAR) Response Criteria [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]
    Response to treatment assessed by EULAR response criteria. Participants were characterized as good, moderate, or non-responders based on both Disease Activity Score (DAS) level attained and change in DAS. Good response defined as >1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders = participants with improvement of ≤0.6 or participants with improvement of >0.6 but ≤1.2 and DAS attained during follow-up of >5.1. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response.

  • Percentage of Participants With American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]
    American College of Rheumatology 20% (ACR20) response: responder = ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.

  • Percentage of Participants With American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]
    American College of Rheumatology 50% (ACR50) response: responder = ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.

  • Percentage of Participants With American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]
    American College of Rheumatology 70% (ACR70) response: responder = ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR) . Subjects withdrawing early were non-responders.

  • Percentage of Participants With American College of Rheumatology 90% (ACR90) Response [ Time Frame: Week 12, Week 24, Week 52 ] [ Designated as safety issue: No ]
    American College of Rheumatology 90% (ACR 90) response: responder = ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.

  • Change From Baseline in Mean Daily Dose of Corticosteroids to Manage Flare-ups Across the 52-week Treatment Period [ Time Frame: Week 4, Week 12, Week 24, Week 40, Week 52 ] [ Designated as safety issue: No ]
    Mean daily dose of corticosteroids to manage flare-ups (temporary increases in corticosteroid dose or use of intra-articular steroids) during treatment period. Daily dose of equivalent prednisone derived in mg/day: oral corticosteroids: 5 mg of prednisone = 5 mg of prednisolone = 25 mg of cortisone = 20 mg of hydrocortisone = 4 mg of methylprednisolone = 4 mg of triamcinolone = 2mg of paramethasone = 0.75 mg of betamethasone = 0.75 of dexamethasone = 0.3 of cortivazol.

  • Percentage of Participants Achieving a Minimal Clinically Important Improvement (MCII) [ Time Frame: Week 12, Week 52 ] [ Designated as safety issue: No ]
    Participants were asked how their pain had been during the last 48 hours compared to baseline. Participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.

  • Percentage of Participants Achieving a Patient Acceptable Symptom State (PASS) [ Time Frame: Week 4, Week 12, Week 24, Week 40, Week 52 ] [ Designated as safety issue: No ]
    Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours.

  • Health Related Quality of Life: EuroQol-5D Health Index [ Time Frame: Baseline, Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]
    EQ-5D is a self-administered questionnaire to assess health-related quality of life in 5 domains (mobility, self care, usual activities, pain or discomfort, and anxiety or depression). Scores from the 5 domains are used to calculate the Health State Profile Score as a single index value; range: 0.0 (death) to 1.0 (perfect health); higher scores indicate a better health state.

  • Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) [ Time Frame: Baseline, Week 12, Week 24, and Week 52 ] [ Designated as safety issue: No ]
    EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.


Enrollment: 141
Study Start Date: September 2008
Study Completion Date: May 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Usual care
Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).
Drug: methotrexate
Active Comparator: ETN + MTX
Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Drug: etanercept (EnbrelTM) Drug: methotrexate

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meet the 1987 ACR Revised Criteria for Rheumatoid Arthritis.
  • Documented evidence, confirmed by a blinded 3rd party assessor, of at least one erosion observed by X-ray at randomization based on X-ray taken at the screening visit.
  • Have received MTX as stable dose for 28 days prior to the screening visit.

Exclusion Criteria:

  • Previous treatment with ETN, infliximab, adalimumab, other Tumor necrosis factor (TNF) -a inhibitors, anakinra or other biological agents.
  • Receipt of any DMARD, other than MTX, within 28 days before screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00706797

  Show 49 Study Locations
Sponsors and Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Wyeth is now a wholly owned subsidiary of Pfizer
  More Information

No publications provided by Wyeth is now a wholly owned subsidiary of Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Director, Clinical Trial Disclosure Group, Wyeth
ClinicalTrials.gov Identifier: NCT00706797     History of Changes
Other Study ID Numbers: 0881X1-4437
Study First Received: June 25, 2008
Results First Received: December 22, 2010
Last Updated: June 16, 2011
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by Wyeth is now a wholly owned subsidiary of Pfizer:
Moderate Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
TNFR-Fc fusion protein
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on August 27, 2014